Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
12740677 A new mathematical model based on clinical and laboratory variables for the diagnosis of S 2003 May Sjögren's syndrome (SS) is a systemic autoimmune disease that mainly affects exocrine glands. A diagnosis of SS in its early stages has a potential clinical relevance, but it is difficult and cannot be made solely on clinical grounds. Several sets of diagnostic criteria have been proposed, but none has met with a general consensus. Minor salivary gland has been judged to be the "gold standard" for the diagnosis of SS. However, it is a painful procedure and has a small but significant proportion of both false positive and false negative results. The aim of our study was to develop a simple mathematical score that uses clinical and laboratory variables for diagnosing SS, thereby reducing the need of minor salivary gland. The following variables were included in the model: ANA, SS-A/SS-B, Schirmer's Test/BUT, C3/C4, serum gammaglobulin levels. One hundred consecutive individuals reporting clinical syndromes consistent with a sicca syndrome were included in the study. The application of our multifactorial mathematical model has shown a high predictive value for SS vs controls or vs patients with other autoimmune disorders (Sensitivity 93%, Specificity 100%), with an estimated minor salivary gland reduction of 77%. We conclude that our mathematical model can be considered a useful non-invasive approach for diagnosing Sjogren's Syndrome and recommend its validation on a larger scale.
11954887 Thrombotic thrombocytopenic purpura as an initial presentation of primary Sjögren's syndr 2002 Feb A healthy woman presented with ecchymoses due to thrombocytopenia, with numerous bone marrow megakaryocytes, microangiopathic haemolytic anaemia, disorientation, irritability, and normal renal function. Thrombotic thrombocytopenic purpura (TTP) was diagnosed and treated successfully by plasma exchange therapy, both on presentation and during a further three relapses. The TTP was considered idiopathic until, 4 months later, definite primary Sjogren's syndrome (1 degree SS) was diagnosed following the appearance of sicca symptoms. Only four similar cases have been cited in the literature. TTP should be added to the varied haematological manifestations that may occur in patients with 1 degree SS. The possible presentation of 1 degree SS not with classic sicca symptoms but rather with haematological abnormalities, including TTP, should be recognised.
15241139 Twenty-year evaluation of cementless mobile-bearing total ankle replacements. 2004 Jul Two consecutive series of patients who had cementless, porous-coated, congruent-contact, mobile-bearing total ankle replacements were evaluated during a 20-year interval using the New Jersey Orthopaedic Hospital ankle scoring scale to determine clinical outcome and overall implant survivorship with revision as an end point. The initial series of 38 patients (40 ankle replacements) using a shallow-sulcus design had diagnoses of: osteoarthritis, seven (17.5%); rheumatoid arthritis, nine (22.5%); posttraumatic arthritis, 21 (52.5%); and failed fusion, three (7.5%). Clinical results after 2-20 years, (mean, 12 years) were 28 (70%) good to excellent, two (5%) fair, and 10 (25%) poor. Postoperative ankle motion ranged from 10 degrees-47 degrees total arc (mean, 25 degrees total arc). The 20-year overall survivorship for the shallow-sulcus design was 74.2%. A second series of 74 patients (75 ankle replacements) using a deep-sulcus design had diagnoses of: osteoarthritis, eight (11%); rheumatoid arthritis, nine (12%); osteonecrosis, three (4%); and posttraumatic arthritis, 55 (73%). Clinical results after 2-12 years, (mean 5 years) were 66 (88%) good to excellent, four (5%) fair, and five (7%) poor. Postoperative ankle motion ranged from 10 degrees-50 degrees total arc (mean, 29 degrees total arc). The 12-year overall survivorship for the deep-sulcus design was 92%.
14979933 Intramuscular electroporation with the pro-opiomelanocortin gene in rat adjuvant arthritis 2004 Endogenous opioid peptides have an essential role in the intrinsic modulation and control of inflammatory pain, which could be therapeutically useful. In this study, we established a muscular electroporation method for the gene transfer of pro-opiomelanocortin (POMC) in vivo and investigated its effect on inflammatory pain in a rat model of rheumatoid arthritis. The gene encoding human POMC was inserted into a modified pCMV plasmid, and 0-200 microg of the plasmid-POMC DNA construct was transferred into the tibialis anterior muscle of rats treated with complete Freund's adjuvant (CFA) with or without POMC gene transfer by the electroporation method. The safety and efficiency of the gene transfer was assessed with the following parameters: thermal hyperalgesia, serum adrenocorticotropic hormone (ACTH) and endorphin levels, paw swelling and muscle endorphin levels at 1, 2 and 3 weeks after electroporation. Serum ACTH and endorphin levels of the group into which the gene encoding POMC had been transferred were increased to about 13-14-fold those of the normal control. These levels peaked 1 week after electroporation and significantly decreased 2 weeks after electroporation. Rats that had received the gene encoding POMC had less thermal hypersensitivity and paw swelling than the non-gene-transferred group at days 3, 5 and 7 after injection with CFA. Our promising results showed that transfer of the gene encoding POMC by electroporation is a new and effective method for its expression in vivo, and the analgesic effects of POMC cDNA with electroporation in a rat model of rheumatoid arthritis are reversed by naloxone.
15168449 [Adult-onset Still disease presenting with disseminated intravascular coagulation]. 2004 Apr A 17-year-old female was admitted to our hospital because of pyrexia and thrombocytopenia in May 2002. Laboratory examination showed a platelet count of 50,000/microliter with an increased level of fibrinogen degradation product, leading to a diagnosis of disseminated intravascular coagulation (DIC). Gabexate mesilate was intravenously administrated without any effects. Several days later, erythema, joint pain and neck lymphadenopathy developed sequentially. The patient was diagnosed as having adult-onset Still disease (AOSD) complicated with DIC. Moreover, serum inflammatory cytokine levels had increased and activated macrophages were observed in the bone marrow, suggesting the presence of macrophage activation syndrome. After additional treatments with dalteparin and aspirin, the clinical symptoms and laboratory findings associated with AOSD and DIC disappeared. Although this was a severe case of AOSD associated with preceding DIC, the AOSD symptoms resolved in this patient with the treatment of the DIC and with aspirin only without any relapse.
17535063 Quality-of-Life Measurements in Juvenile Rheumatoid Arthritis Patients Treated with Etaner 2003 OBJECTIVE: The aims of this study were: (1) to assess functional status, emotional well-being and quality of life in patients with polyarticular and systemic juvenile rheumatoid arthritis (JRA) treated with etanercept, and (2) to determine the prevalence and significance of adverse events associated with etanercept therapy. PATIENTS AND METHODS: All JRA patients (n = 21) who received etanercept in our rheumatology clinic over a 14-month period were evaluated. Patient demo-graphics, type of arthritis, dosing regimens, family history, measures of joint function and laboratory parameters were obtained for each patient. A questionnaire that comprised validated functional assessment and quality-of-life measures (the Childhood Health Assessment Questionnaire [CHAQtrade mark], the Juvenile Arthritis Function Assessment Report [JAFAR 5trade mark] and the Pediatric Quality of Life Inventory Version 4 [PedsQL Generic Scaletrade mark] scales) was administered to patients and parents to assess physical and emotional function, pain, adverse drug events and quality of life at each clinic visit. RESULTS: Functional status and quality of life improved in patients with poly-articular and systemic disease. A significant difference between pre- and post-etanercept functional assessment (JAFARtrade mark and CHAQtrade mark) and quality-of-life assessment by parents and patients was found (p = 0.009, p = 0.002, p
11807193 Adult Still's disease and respiratory failure in a 74 year old woman. 2002 Feb A case of adult onset Still's disease in an elderly woman, that was associated with severe respiratory failure and multiorgan dysfunction, is reported. Histopathology was confirmed on open lung biopsy.
15460090 A primary care approach to Sjögren's syndrome. Helping patients cope with sicca symptoms, 2004 Sep Sjögren's syndrome is a chronic, systemic, autoimmune inflammatory disorder characterized by lymphocytic infiltration of exocrine glands, most notably the salivary and lacrimal glands. It results in loss of functional epithelium, diminished exocrine function, and gradual onset of dryness of the eyes, mouth, and other body parts (sicca syndrome). Because most patients with Sjögren's syndrome are female, this syndrome also represents a major women's health problem that is often misdiagnosed and undertreated. In this article, Drs Derk and Vivino review the criteria for diagnosis, common signs and symptoms, and strategies for increasing patient comfort.
15554367 [Primary Sjögren's syndrome and hypokalaemic paralysis--case report]. 2004 We report a case of hypokalaemic quadriparesis in 31-year old woman in whom the discovery of distal renal tubular acidosis led to the diagnosis of primary Sjögren's syndrome. Hypokalaemic paralysis as initial manifestation of primary Sjögren's syndrome is rare, but when it occurs it may precede symptoms of xerostomia and xerophthalmia. The diagnosis of primary Sjögren's syndrome should be considered in young women who present with progressive weakness, hypokalaemia and metabolic acidosis.
15188603 [Tumor necrosis factor-alpha in tears of patients with Sjögren syndrome]. 2004 May PURPOSE: To determine the pathological role of tumor necrosis factor alpha (TNF-alpha) in ocular surface disorder of patients with Sjögren syndrome (SS), TNF-alpha in the tears of patients with SS were analyzed. In addition, the relationship between TNF-alpha levels in the tear samples and the severity of the corneal epithelial disorder was evaluated. MATERIAL AND METHODS: Tear samples were obtained from the 60 eyes of 30 patients with primary SS and the 60 eyes of 30 normal subjects. Tear samples were analyzed using a sandwich enzyme-linked immunosorbent assay to detect TNF-alpha. Corneal epithelial cell damage was examined with a slit-lamp biomicroscope and scored by the van Bijsterveld scoring system. RESULTS: TNF-alpha was detected in the tears of patients with SS at concentrations ranging from 8 to 1,500 pg/ml in 33 of the 60 eyes of the patients. In contrast, TNF-alpha was not detected in the tears of normal controls. The concentration of TNF-alpha was significantly higher in the tear samples from patients whose clinical scores were two or three points compared with patients whose scores were zero or one point (Mann-Whitney U test: p < 0.03). CONCLUSIONS: TNF-alpha was detected in the tears of patients with SS, and tear TNF-alpha levels showed a significant correlation with the grade of corneal epithelial damage, suggesting that TNF-alpha is a potent mediator in keratoconjunctivitis sicca.
14687716 Advances in vector-mediated gene transfer. 2003 Dec 15 Clinical applications of gene transfer technology initially targeted the treatment of inherited monogenetic disorders and cancers refractory to conventional therapies. Today, gene transfer approaches are being developed for most tissues and for multiple disorders including those affecting quality of life. The focus herein is eventual application of gene transfer technology for the management of organ-directed autoimmunity. A specific example is presented: Sjögren's syndrome and localized salivary gland gene transfer. The status of relevant pre-clinical gene transfer studies is reviewed, with an emphasis on use of adenoviral and adeno-associated viral vectors. Current limitations of effective organ-directed gene transfer are also discussed.
12508393 Comprehensive study of autonomic function in a population with primary Sjögren's syndrome 2003 Jan OBJECTIVE: Autonomic neuropathy is associated with increased mortality. Autonomic nervous system disorders have been described in patients with primary Sjögren's syndrome (SS), but the results in controlled studies have been contradictory, varying from normal to sympathetic or parasympathetic dysfunction. Since the earlier studies employed varying methodologies, which may have led to the discrepancy, we conducted a comprehensive study on autonomic function in patients with primary SS and compared our findings to healthy, carefully matched population based controls. METHODS: A conventional cardiovascular reflex test battery (Valsalva maneuver, deep breathing test, active orthostatic test) and measurements of baroreflex sensitivity with phenylephrine and 24 hour heart rate variability were performed on 30 patients with primary SS and 30 healthy age and sex matched population based controls. RESULTS: There were no significant differences between the SS patients and the healthy controls in any of the tests. CONCLUSIONS: The prevalence of autonomic dysfunction is not increased in patients with primary SS compared to the general population.
12240717 Isolated autonomic cardiovascular neuropathy in a patient with primary Sjögren syndrome: 2002 Sep Autonomic failure is rare in patients with Sjögren syndrome (SS). We report the case of a 46-year-old woman with severe autonomic cardiovascular failure, manifested by incapacitating postural hypotension, as the first symptom of primary SS. Treatment with glucocorticoid resulted in a dramatic improvement of her symptoms and objective findings of autonomic cardiovascular dysfunction. We suggest that SS should be considered in patients with idiopathic autonomic cardiovascular neuropathy, especially in those with idiopathic orthostatic hypotension. Furthermore, glucocorticoid therapy seems to be very efficacious in the treatment of SS-associated autonomic cardiovascular neuropathy.
12913947 Classification of juvenile idiopathic arthritis: should family history be included in the 2003 Aug OBJECTIVE: (i) To determine the efficacy of the Durban classification for children with juvenile idiopathic arthritis (JIA) where < 5 joints were involved at onset (with systemic arthritis excluded) by determining the proportion of the cohort that proved to be "unclassifiable"; (ii) to define reasons for cases being "unclassifiable," particularly regarding family history; and (iii) to compare the efficacy of a proposed hierarchical system (an unofficial modification of the Durban classification) with the Durban classification, where family history details are included as descriptors, rather than as classification criteria. METHODS: Charts were reviewed of 50 children with fewer than 5 joints involved at presentation for JIA, followed for at least 12 months, with systemic arthritis excluded. Cases were classified according to the EULAR criteria, the Durban criteria, and by a proposed "modified Durban" classification subject to hierarchy, with exclusions in the following order: systemic arthritis, rheumatoid factor (RF) positive arthritis, psoriasis or a combination of dactylitis and psoriatic nail changes (psoriatic arthritis), and HLA-B27 positive arthritis (enthesitis related arthritis), with the remainder of children being classified as having either RF negative polyarthritis or RF negative oligoarthritis, depending on number of joints involved, with additional information noted as descriptors. The "modified Durban" classification was proposed only to stimulate discussion among clinicians. RESULTS: Of 50 children, 56% were "unclassifiable" by the Durban classification, mainly because of inadequate family history despite appropriate questioning. Using the proposed "modified Durban" classification, 2% were "unclassifiable." Family history was classified as inadequate for the following reasons: The parents did not know family history; the child or parent was adopted; the father was unknown or parent died early; parents never attended; extended family had lost communication with parents; or a relative was considered to have psoriasis, but not confirmed by dermatologists. Other reasons for "unclassifiable" included: dermatologists unable to confirm psoriasis; family history of inflammatory bowel disease and sacroiliitis but B27 status unknown; proband B27 negative but family history of B27-related disease; family history of psoriasis, but patient had insufficient criteria for psoriatic arthritis and therefore excluded from oligoarthritis, psoriatic arthritis and other groups. CONCLUSION: (i) The Durban classification showed poor efficacy for JIA where < 5 joints were involved at onset, with more than half the cases being "unclassifiable". (ii) The most common reason was that appropriate family history was not available despite being sought by the clinician. (iii) A proposed hierarchical system, an unofficial modification of the Durban classification, showed good efficacy, with only one of 50 cases being "unclassifiable."
17143663 Pharmacokinetics and efficacy of low-dose methotrexate in patients with rheumatoid arthrit 2004 This article evaluates the relationship between the pharmacokinetics of methotrexate (MTX), its efficacy in the treatment of rheumatoid arthritis (RA), and serum folic acid (FA) levels. The pharmacokinetics of MTX was studied in 29 patients with RA treated with low-dose MTX. The weekly dose of MTX was given orally at 2-4 mg every 12 h over a period of 24-36 h. Blood samples were taken 4 h after the first administration in any given week. A Bayesian method was used to estimate individual MTX pharmacokinetic variables. We then investigated the efficacy of MTX and the serum FA levels in these patients. We examined C-reactive protein levels (CRP) and the erythrocyte sedimentation rate (ESR), and analyzed the values obtained before and after MTX treatment in order to evaluate the efficacy of the MTX treatment. The degree of improvement in CRP and ESR was significantly correlated with the length of time the MTX concentration-time curve remained above 0.02 microM in one week. Furthermore, the degree of improvement in CRP was also significantly correlated with the area under the concentration-time curve (AUC) for MTX. These results suggest that serum MTX measurements could be useful in determining individual patient regimens.
11858777 Cardiovascular Complications of Collagen Vascular Disease. 2002 Apr Collagen vascular diseases commonly affect the heart; cardiovascular events are the major cause of mortality in people with these diseases. A striking feature of the cardiac involvement in individuals with systemic lupus erythematosus (SLE) and rheumatoid arthritis is aggressive and accelerated atherosclerosis; women with SLE in the 35- to 44-year-old age group are more than 50 times more likely to suffer myocardial infarction than are matched controls. Traditional risk factors contribute to the accelerated atherosclerosis, but cannot explain the extent of risk. It is possible that the inflammatory process, which is similar to the inflammatory process in atherosclerosis, pays a critical pathophysiologic role. It is critically important to identify the presence of traditional cardiovascular risk factors (eg, tobacco usage, hypertension, hypercholesterolemia, diabetes, homocysteinemia), and to modify these to secondary prevention targets. Cardiac valvular disease is common in individuals with SLE and rheumatoid arthritis; its presence should be anticipated and subacute bacterial endocarditis prophylaxis precautions initiated. Cardiac autonomic neuropathy and conduction disturbances are common in people with heart disease related to systemic sclerosis and human leukocyte antigen B27; these patients should be monitored carefully for evidence of dysrhythmias.
17043483 Sepsis as a possible adverse drug reaction in patients with rheumatoid arthritis treated w 2004 Jun BACKGROUND: Clinical improvement during the treatment of rheumatoid arthritis (RA) with the TNFalpha antagonists has been well documented. Our knowledge of uncommon adverse drug reactions (ADRs) with these new drugs is more restricted. Concerns have been raised that these types of drugs could cause an increased frequency of infections, and already existing infections are named as contraindications in the product labels. METHODS: In Sweden, it is compulsory for healthcare professionals with permission to prescribe drugs to report suspected ADRs to the regulatory authority, the Medical Product Agency (MPA). At the 6 regional centers that are established in Sweden, a preliminary causality assessment is made and the data is transferred online to a database. RESULTS: Between January 1, 1999, and June 30, 2003, 29 cases of sepsis were reported as suspected adverse effects caused by drugs. Seventeen of these cases concerned TNFalpha antagonists. The MPA has received 3 reports of septicemia in patients from Northern Sweden treated with the TNFalpha antagonist etanercept. In submitting these reports, factors that can contribute to susceptibility and to more fatal courses of serious infections are taken into consideration. Demographic and pharmaceutical factors as well as risks from predisposing conditions are discussed in connection with the cases in this report. CONCLUSION: There is a need for more information to physicians to be aware of sepsis as a possible and serious ADR during treatment with TNF antagonists, and that patients with predisposing diseases or those who do not regularly visit their rheumatologist could be at higher risk.
17041974 Occupational balance of women with rheumatoid arthritis: a qualitative study. 2004 OBJECTIVE: Occupational balance has been shown to be an important factor in maintaining health. Rheumatoid arthritis (RA) reduces functional ability and quality of life and may thus reduce occupational balance. The aim of this qualitative pilot study was to explore occupational balance in women who have RA. METHODS: Nine women with RA with past, but not current, paid work experience, no other confounding neuro-motor disease and with disease duration of 0.75-31 years were selected from an Austrian rheumatology outpatient clinic. Age range of the participants was 28-68 years. A semi-structured interview was conducted with each participant and transcribed verbatim. Data were analysed by the constant comparative method from an occupational perspective. RESULTS: Three main categories emerged: (1) The participants experienced a process of change that affected their occupational balance. (2) This new state of occupational balance was characterized by changed levels of involvement in physical, mental, social and rest occupations and by a certain level of unpredictability of symptoms. (3) Overall, the new state of occupational balance was valued differently: positively, indifferently or negatively. CONCLUSION: RA was found to have a considerable impact on occupational balance. The experience is not invariably seen as negative as previous literature would suggest. Further research should explore the longitudinal dimension of occupational balance in people with RA.
17041450 The decreasing prevalence of uveitis associated with juvenile rheumatoid arthritis: do NSA 2003 Jun We studied the prevalence and characteristics of chronic uveitis in a population of children diagnosed with juvenile rheumatoid arthritis (JRA). Uveitis is one of the most important, potentially debilitating extra-articular manifestations of JRA and has been observed in as many as 20% of cases. The medical records of 230 patients diagnosed with JRA and treated at a tertiary care hospital ophthalmology clinic between 1992 and 2000 were retrospectively reviewed. Seventeen patients (7.4%) were found to have clinical features of uveitis. There was a preponderance of female patients (16/17) and pauciarticular disease (13/17). Only 12 of 17 were ANA positive. Six had uveitis at diagnosis. Patients who were receiving naproxen had less incidence of uveitis compared with those receiving other nonsteroidal antiinflammatory drugs. Despite a relatively low prevalence of uveitis, complications occurred in about 24% (4/17) of the patients, even with adequate treatment and close monitoring. The prevalence of uveitis in JRA seems to be decreasing and may be secondary to the increased use of naproxen. However, routine ophthalmologic screening should be continued in patients with JRA to avoid potential complications of chronic uveitis.
15314502 Neoantigens in osteoarthritic cartilage. 2004 Sep PURPOSE OF REVIEW: Osteoarthritis has been considered a degenerative disease. However, recent evidence supports involvement of immunologic mechanisms in this pathophysiology: for example, inflammation of synovial tissue is observed in osteoarthritis. In osteoarthritis, the proinflammatory cytokine interleukin-1, which is produced by activated synoviocytes and mononuclear cells and has catabolic effects on chondrocytes, is one of the most involved. The immune reaction would require driving antigens. This review describes autoantigens in osteoarthritis and discusses their roles in triggering and/or perpetuating synovitis and joint cartilage destruction in osteoarthritis. RECENT FINDINGS: Several autoantigens/autoantibodies have been reported in osteoarthritis, such as the cartilage intermediate layer protein. Furthermore, recent comprehensive proteomic surveillance has revealed that comparable numbers of autoantigens were detected in osteoarthritis and rheumatoid arthritis, and that some of them were recognized predominantly in osteoarthritis rather than in rheumatoid arthritis. In addition, it was revealed that the cartilage intermediate layer protein immunization of mice developed calcification of tendons, thus indicating that autoimmunity modulates functions of target molecules. SUMMARY: Osteoarthritis-specific autoantigens may drive chronic synovitis and may thereby contribute to production of cytokines to upregulate proteases, which lead to chondrocyte and cartilage damage. In addition, autoimmunity may damage joint components by modulating functions of the target molecules.